EP2328593B1 - Kardioplegische zubereitung - Google Patents
Kardioplegische zubereitung Download PDFInfo
- Publication number
- EP2328593B1 EP2328593B1 EP09736485.5A EP09736485A EP2328593B1 EP 2328593 B1 EP2328593 B1 EP 2328593B1 EP 09736485 A EP09736485 A EP 09736485A EP 2328593 B1 EP2328593 B1 EP 2328593B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- solution
- cardioplegic
- preparation
- solutions
- dose
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000002360 preparation method Methods 0.000 title claims description 20
- 230000001101 cardioplegic effect Effects 0.000 title claims description 10
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 6
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 239000000811 xylitol Substances 0.000 claims description 6
- 229960002675 xylitol Drugs 0.000 claims description 6
- 235000010447 xylitol Nutrition 0.000 claims description 6
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M potassium chloride Inorganic materials [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 5
- 229960001309 procaine hydrochloride Drugs 0.000 claims description 5
- 229960002303 citric acid monohydrate Drugs 0.000 claims description 4
- 229940061634 magnesium sulfate heptahydrate Drugs 0.000 claims description 4
- 239000001103 potassium chloride Substances 0.000 claims description 4
- 235000011164 potassium chloride Nutrition 0.000 claims description 4
- YASYEJJMZJALEJ-UHFFFAOYSA-N Citric acid monohydrate Chemical compound O.OC(=O)CC(O)(C(O)=O)CC(O)=O YASYEJJMZJALEJ-UHFFFAOYSA-N 0.000 claims description 3
- 239000000243 solution Substances 0.000 description 31
- 239000008148 cardioplegic solution Substances 0.000 description 6
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 6
- 229960004919 procaine Drugs 0.000 description 6
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 5
- 230000000747 cardiac effect Effects 0.000 description 5
- 239000011591 potassium Substances 0.000 description 5
- 229910052700 potassium Inorganic materials 0.000 description 5
- 238000007675 cardiac surgery Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 230000002980 postoperative effect Effects 0.000 description 3
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 208000010496 Heart Arrest Diseases 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 210000004351 coronary vessel Anatomy 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000002107 myocardial effect Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 206010059484 Haemodilution Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 208000035965 Postoperative Complications Diseases 0.000 description 1
- HCBIBCJNVBAKAB-UHFFFAOYSA-N Procaine hydrochloride Chemical compound Cl.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 HCBIBCJNVBAKAB-UHFFFAOYSA-N 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000005003 heart tissue Anatomy 0.000 description 1
- 230000002727 hyperosmolar Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 208000037906 ischaemic injury Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- WRUGWIBCXHJTDG-UHFFFAOYSA-L magnesium sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Mg+2].[O-]S([O-])(=O)=O WRUGWIBCXHJTDG-UHFFFAOYSA-L 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 229940052264 other local anesthetics in atc Drugs 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
- A61K31/24—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
- A61K31/245—Amino benzoic acid types, e.g. procaine, novocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Definitions
- the invention relates to cardiac surgery. It more precisely concerns a cardioplegic preparation which can be used during cardiac surgery.
- the invention relates to a dose of a cardioplegic preparation containing at least magnesium and potassium and more precisely to a dose as defined in the claims.
- the preparation is initially made of two separate solutions, the first containing said magnesium component and the second containing local anesthetics, e.g. procaine.
- the two separate solutions are containing the following components: Solution A: - Magnesium - Potassium - Xylitol Solution B: - Procaine
- the solutions are buffered so that the pH after mixture of both solutions is between 5.5 and 7.0
- Solution A - Magnesium sulfate heptahydrate - Potassium chloride - Xylitol
- Solution B - Procaine hydrochloride
- Variations can include the following added component:
- the dose according to the invention is defined as follows: Solution A: - Magnesium sulfate heptahydrate 3-5 g - Potassium chloride 0.1 -1.0 g - Xylitol 1-10 g Solution B: - Procaine hydrochloride 0.1 - 1.0 g
- Water is used to have a final volume (solution A + solution B) of 20 to 250 ml.
- Solution A is buffered with citric acid monohydrate to a pH of 5.5 to 7.0.
- the dose is defined as follows :
- Solution A Magnesium sulfate heptahydrate 4g 16.2 mmol Potassium chloride 0.746 g 10.0 mmol Xylitol 4.5 g 29.6 mmol Citric acid monohydrate 1.061 g 5.0 mmol Water for injection to a final volume of 95 ml
- Solution B Procaine hydrochloride 0.3 g 1.1 mmol Water for injection to a final volume of 5 ml
- pH of the mixed ready to use solution is 6.0.
- the preparation is hyperosmolar with an osmolarity of the mixed ready to use solution of approximately 850 mosmol/l.
- the preparation according to the invention offers the advantage of avoiding the known incompatibility between procaine and sulfate. Importantly, the tests have also demonstrated that at 2-8 °C and within the first 60 minutes following the mixing of solutions A and B, this incompatibility is not relevant.
- the preparation according to the invention has a higher potassium concentration.
- Experimental and clinical tests have both confirmed a reduced bioavailability of Potassium ions when in presence of xylitol and/or citric acid. By increasing thus the initial content of potassium in the cardioplegic solution, the concentration necessary to achieve the cardioplegic effect is guaranteed. In addition, clinical tests have confirmed that no potassium overdose is achieved.
- pH is also reduced to 6.0 which interestingly and advantageously allows to increase the effect of procaine.
- Solution A is prepared in a sterile way and stored in a vial with 95 ml.
- Solution B is also prepared in a sterile way and separately stored in a light protected 5 ml syringe.
- the solutions are stored at 2-8 °C.
- the ready to use solution (100 ml) is obtained by injecting the content of the syringe (solution B, 5 ml) into the vial (solution A, 95 ml). This resulting mixture is administered within 60 minutes after mixing, preferably within 15 minutes after mixing.
- the preparation according to the invention was tested in several patients.
- the combination of the compounds was even tested in more than 3'000 patients and showed clear advantages as compared to traditional cardioplegic solutions.
- the administration is simplified, but the cardiac arrest is almost instantaneous allowing thus the surgeon to immediately focus on his surgical procedure.
- the surgeon has to deliver a much larger quantity of solution and wait up to 5 minutes until the heart is considered ready to be operated on.
- the current solution allows arrest and protection usually for more than 45-60 minutes whereas other solutions traditionally need to be repeated every 20 minutes.
- Clinical results are significantly superior since several of the post-operative complications can be reduced such as the rate of post-operative cardiac arythmias.
- the preparation according to the invention can be integrated in the concept of new extra corporeal circulation (ECC) machines which aim to reduce or eliminate the trauma of such devices.
- ECC extra corporeal circulation
- cardioplegic preparation according to the invention presents several significant advantages, in particular :
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Inorganic Chemistry (AREA)
- Molecular Biology (AREA)
- Emergency Medicine (AREA)
- Dermatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Claims (2)
- Dosis eines kardioplegischen Präparats, umfassend:
- Lösung A: - Magnesiumsulfatheptahydrat 3-5 g - Kaliumchlorid 0,1-1,0 g - Xylit 1-10 g - Lösung B: - Procain-hydrochlorid 0,1-1,0 g - Wasser, - Dosis eines kardioplegischen Präparats nach Anspruch 1, wobei das folgende Präparat verwendet wird:
- Lösung A: - Magnesiumsulfatheptahydrat 4 g - Kaliumchlorid 0,746 g - Xylit 4, 5 g - Zitronensäure-monohydrat 1,061 g - Wasser auf ein Endvolumen von 95 ml - Lösung B: - Procain-hydrochlorid 0, 3 g - Wasser auf ein Endvolumen von 5 ml.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PL09736485T PL2328593T3 (pl) | 2008-08-22 | 2009-08-10 | Kardioplegiczny preparat |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IB2008053377 | 2008-08-22 | ||
PCT/IB2009/053505 WO2010020904A2 (en) | 2008-08-22 | 2009-08-10 | Cardioplegic preparation |
Publications (2)
Publication Number | Publication Date |
---|---|
EP2328593A2 EP2328593A2 (de) | 2011-06-08 |
EP2328593B1 true EP2328593B1 (de) | 2014-12-31 |
Family
ID=41533755
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP09736485.5A Active EP2328593B1 (de) | 2008-08-22 | 2009-08-10 | Kardioplegische zubereitung |
Country Status (7)
Country | Link |
---|---|
US (1) | US9763979B2 (de) |
EP (1) | EP2328593B1 (de) |
CN (1) | CN102131510A (de) |
ES (1) | ES2533475T3 (de) |
PL (1) | PL2328593T3 (de) |
PT (1) | PT2328593E (de) |
WO (1) | WO2010020904A2 (de) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
RU2706017C1 (ru) * | 2019-02-01 | 2019-11-13 | Федеральное государственное бюджетное военное образовательное учреждение высшего образования "Военно-медицинская академия имени С.М. Кирова" Министерства обороны Российской Федерации (ВМедА) | Способ комбинированной защиты миокарда и устройство для выполнения кровяной холодовой кардиоплегии при операциях на сердце у новорожденных и детей грудного возраста |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SE8403912D0 (sv) * | 1984-07-30 | 1984-07-30 | Pharmacia Ab | Lekemedelssats eller -komposition |
EP1996181A1 (de) * | 2006-03-15 | 2008-12-03 | Universität Bern | Kardioplege lösung |
-
2009
- 2009-08-10 PT PT97364855T patent/PT2328593E/pt unknown
- 2009-08-10 US US13/059,517 patent/US9763979B2/en active Active
- 2009-08-10 ES ES09736485.5T patent/ES2533475T3/es active Active
- 2009-08-10 EP EP09736485.5A patent/EP2328593B1/de active Active
- 2009-08-10 WO PCT/IB2009/053505 patent/WO2010020904A2/en active Application Filing
- 2009-08-10 PL PL09736485T patent/PL2328593T3/pl unknown
- 2009-08-10 CN CN2009801326674A patent/CN102131510A/zh active Pending
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
RU2706017C1 (ru) * | 2019-02-01 | 2019-11-13 | Федеральное государственное бюджетное военное образовательное учреждение высшего образования "Военно-медицинская академия имени С.М. Кирова" Министерства обороны Российской Федерации (ВМедА) | Способ комбинированной защиты миокарда и устройство для выполнения кровяной холодовой кардиоплегии при операциях на сердце у новорожденных и детей грудного возраста |
Also Published As
Publication number | Publication date |
---|---|
US9763979B2 (en) | 2017-09-19 |
ES2533475T3 (es) | 2015-04-10 |
US20110183010A1 (en) | 2011-07-28 |
PT2328593E (pt) | 2015-04-13 |
WO2010020904A3 (en) | 2010-07-22 |
PL2328593T3 (pl) | 2015-08-31 |
CN102131510A (zh) | 2011-07-20 |
EP2328593A2 (de) | 2011-06-08 |
WO2010020904A2 (en) | 2010-02-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Tassani et al. | Does high-dose methylprednisolone in aprotinin-treated patients attenuate the systemic inflammatory response during coronary artery bypass grafting procedures? | |
JP5107053B2 (ja) | 急性腎不全の予防または治療剤 | |
EA019258B1 (ru) | КОМПОЗИЦИИ, СОДЕРЖАЩИЕ МОДУЛЯТОРЫ ФАКТОРА КОАГУЛЯЦИИ VIIa, И ИХ ПРИМЕНЕНИЕ | |
JP5684954B1 (ja) | 安定性を改善したロクロニウム製剤 | |
JP2014185161A (ja) | シロスタゾールを含むカルボスチリル誘導体の脂肪肝治療剤 | |
US10987378B2 (en) | Universal cardioplegic solution (variants) | |
KR101434329B1 (ko) | 체온 저하 억제제 | |
CA2500310C (en) | Method for cardioprotection and neuroprotection by intravenous administration of halogenated volatile anesthetics | |
EP2328593B1 (de) | Kardioplegische zubereitung | |
EP2106791A1 (de) | Glutamin oder Glutamine enthaltendes Dipeptide in einer spezifischen Dosierung für die Behandlung von Entzündungen | |
CN106421746A (zh) | [Pyr1]‑Apelin‑13 作为长效酰胺类局麻药中毒所致心脏停搏的抢救药物的应用 | |
KR20210126515A (ko) | 니클로사마이드를 포함하는 폐고혈압의 예방 및 치료용 조성물 | |
Kim et al. | Successful management of potential non-heart-beating donor with extracorporeal membrane oxygenation: A case report | |
KR20150047515A (ko) | 관상동맥 우회로 이식술이 예정된 환자의 st 비상승 급성 관상동맥 증후군 치료에 사용되는 오타믹사반 | |
Hirata et al. | Hyperkalemia by Euro-Collins solution in anesthesia for renal transplantation: a case report | |
Kim et al. | Successful Management of Potential Non-Heart-Beating Donor with Extracorporeal Membrane Oxygenation | |
Kakinohana et al. | Patient-controlled sedation using propofol in eight patients with endstage renal failure. | |
Hopgood et al. | Postoperative care | |
JP2002538119A (ja) | 血圧低下のためのレミフェンタニルの使用 | |
KR20080109044A (ko) | 락테이트 및 칼슘 함유 약학 조성물 및 그의 용도 | |
Saleh et al. | controlled hypotension in endoscopic sinus surgery: comparative study between the efficacy of esmolol, sodium nitroprusside and magnesium sulphate | |
Guleria et al. | Dr Manjit Singh Kanwar | |
KR20160030191A (ko) | 뇌 및 전신의 재관류 손상을 예방하거나 감소시키기 위한 보호 용액 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 20110322 |
|
AK | Designated contracting states |
Kind code of ref document: A2 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO SE SI SK SM TR |
|
AX | Request for extension of the european patent |
Extension state: AL BA RS |
|
DAX | Request for extension of the european patent (deleted) | ||
17Q | First examination report despatched |
Effective date: 20130503 |
|
GRAP | Despatch of communication of intention to grant a patent |
Free format text: ORIGINAL CODE: EPIDOSNIGR1 |
|
INTG | Intention to grant announced |
Effective date: 20140722 |
|
GRAS | Grant fee paid |
Free format text: ORIGINAL CODE: EPIDOSNIGR3 |
|
GRAA | (expected) grant |
Free format text: ORIGINAL CODE: 0009210 |
|
AK | Designated contracting states |
Kind code of ref document: B1 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO SE SI SK SM TR |
|
REG | Reference to a national code |
Ref country code: GB Ref legal event code: FG4D Ref country code: CH Ref legal event code: EP |
|
REG | Reference to a national code |
Ref country code: IE Ref legal event code: FG4D |
|
REG | Reference to a national code |
Ref country code: AT Ref legal event code: REF Ref document number: 703960 Country of ref document: AT Kind code of ref document: T Effective date: 20150215 |
|
REG | Reference to a national code |
Ref country code: DE Ref legal event code: R096 Ref document number: 602009028692 Country of ref document: DE Effective date: 20150219 |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: NV Representative=s name: ANDRE ROLAND S.A., CH |
|
REG | Reference to a national code |
Ref country code: NL Ref legal event code: T3 |
|
REG | Reference to a national code |
Ref country code: ES Ref legal event code: FG2A Ref document number: 2533475 Country of ref document: ES Kind code of ref document: T3 Effective date: 20150410 |
|
REG | Reference to a national code |
Ref country code: PT Ref legal event code: SC4A Free format text: AVAILABILITY OF NATIONAL TRANSLATION Effective date: 20150323 |
|
REG | Reference to a national code |
Ref country code: SE Ref legal event code: TRGR |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: NO Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20150331 Ref country code: FI Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20141231 Ref country code: LT Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20141231 |
|
REG | Reference to a national code |
Ref country code: LT Ref legal event code: MG4D |
|
REG | Reference to a national code |
Ref country code: GR Ref legal event code: EP Ref document number: 20150400701 Country of ref document: GR Effective date: 20150421 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: HR Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20141231 Ref country code: LV Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20141231 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: SK Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20141231 Ref country code: RO Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20141231 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: IS Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20150430 |
|
REG | Reference to a national code |
Ref country code: PL Ref legal event code: T3 |
|
REG | Reference to a national code |
Ref country code: DE Ref legal event code: R097 Ref document number: 602009028692 Country of ref document: DE |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: EE Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20141231 Ref country code: DK Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20141231 |
|
PLBE | No opposition filed within time limit |
Free format text: ORIGINAL CODE: 0009261 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT |
|
26N | No opposition filed |
Effective date: 20151001 |
|
REG | Reference to a national code |
Ref country code: AT Ref legal event code: UEP Ref document number: 703960 Country of ref document: AT Kind code of ref document: T Effective date: 20141231 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: SI Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20141231 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LU Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20150810 Ref country code: MC Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20141231 |
|
REG | Reference to a national code |
Ref country code: IE Ref legal event code: MM4A |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: IE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20150810 |
|
REG | Reference to a national code |
Ref country code: FR Ref legal event code: PLFP Year of fee payment: 8 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: MT Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20141231 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: HU Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT; INVALID AB INITIO Effective date: 20090810 Ref country code: SM Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20141231 Ref country code: BG Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20141231 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: CY Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20141231 |
|
REG | Reference to a national code |
Ref country code: FR Ref legal event code: PLFP Year of fee payment: 9 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: MK Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20141231 |
|
REG | Reference to a national code |
Ref country code: FR Ref legal event code: PLFP Year of fee payment: 10 |
|
P01 | Opt-out of the competence of the unified patent court (upc) registered |
Effective date: 20230530 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: NL Payment date: 20230821 Year of fee payment: 15 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: TR Payment date: 20230808 Year of fee payment: 15 Ref country code: IT Payment date: 20230825 Year of fee payment: 15 Ref country code: GB Payment date: 20230822 Year of fee payment: 15 Ref country code: CZ Payment date: 20230731 Year of fee payment: 15 Ref country code: CH Payment date: 20230902 Year of fee payment: 15 Ref country code: AT Payment date: 20230822 Year of fee payment: 15 |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: SPCF Free format text: PRODUCT NAME: MAGNESII SULFAS HEPTAHYDRICUS, KALII CHLORIDUM, XYLITOLUM, PROCAINI HYDROCHLORIDUM; REGISTRATION NO/DATE: SWISSMEDIC-ZULASSUNG 68015 01 31.08.2023 Filing date: 20231026 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: SE Payment date: 20230821 Year of fee payment: 15 Ref country code: PT Payment date: 20230727 Year of fee payment: 15 Ref country code: PL Payment date: 20230727 Year of fee payment: 15 Ref country code: GR Payment date: 20230822 Year of fee payment: 15 Ref country code: FR Payment date: 20230824 Year of fee payment: 15 Ref country code: DE Payment date: 20230821 Year of fee payment: 15 Ref country code: BE Payment date: 20230821 Year of fee payment: 15 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: ES Payment date: 20231027 Year of fee payment: 15 |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: SPCC Spc suppl protection certif: C02328593 Ref country code: CH Ref legal event code: SPCG Free format text: PRODUCT NAME: MAGNESII SULFAS HEPTAHYDRICUS, KALII CHLORIDUM, XYLITOLUM, PROCAINI HYDROCHLORIDUM; REGISTRATION NO/DATE: SWISSMEDIC-ZULASSUNG 68015 31.08.2023 Spc suppl protection certif: C02328593/01 Filing date: 20231026 Extension date: 20340809 |